Familial Hypercholesterolemia (FH) is a hereditary lipid disorder caused by pathogenic mutations affecting LDL receptor function, apolipoprotein B, or PCSK9 pathways. These genetic defects impair hepatic clearance of LDL cholesterol, resulting in markedly elevated LDL-C levels from birth and accelerated atherosclerosis.

FH follows an autosomal dominant inheritance pattern and is classified as heterozygous or homozygous, with homozygous forms presenting more severe disease and extremely early cardiovascular events. If untreated, individuals with FH may develop coronary artery disease in early adulthood or even childhood.

Clinically, FH is suspected in patients with persistently elevated LDL cholesterol levels (>190 mg/dL in adults), family history of premature cardiovascular disease, or physical signs such as tendon xanthomas, xanthelasma, or corneal arcus at a young age. However, many patients lack overt physical findings, leading to underdiagnosis.

Diagnosis relies on lipid profiling, clinical scoring systems (such as Dutch Lipid Clinic criteria), family screening, and genetic testing when available. Cascade screening of first-degree relatives is a cornerstone of FH management to enable early detection and prevention.

Treatment requires early, aggressive, and lifelong lipid-lowering therapy. High-intensity statins are foundational, often combined with ezetimibe or PCSK9 inhibitors to achieve LDL-C targets. Lifestyle measures alone are insufficient due to the genetic nature of the condition. With appropriate treatment, cardiovascular risk can be dramatically reduced, emphasizing the importance of early diagnosis.